Intervertebral total disc replacement (TOR) implants potentially herald a paradigm shift in the management of degenerative disc disease. Preservation of motion may avoid adjacent-segment degeneration, a well-recognized complication effusion. Based on encouraging experience in Europe and now-concluding IDE trials, FDA approval is likely in early/mid 2005 for two leading designs: Charite III and ProDisc. As an alternative to fusion (approximately 330,000/year in the U.S.), an onrush of implantations of these devices seems imminent. The potential for late wear-related complications is concerning. Both devices involve metal-on-conventional-polyethylene bearings, and the TDR patient population is a decade younger than for THR/TKR. Moreover, owing to close proximity of the spinal cord, the potential consequences of implant failure are much more dire than for THR/TKR. It is crucial that the scientific community expeditiously confront the issue of TDR wear. A Bioengineering Research Partnership is proposed to provide a firm scientific basis for identifying and dealing with wear-related problems in TDR. Aim 1 is to develop techniques for TDR wear assessment in the pre-clinical phase. This will be done leveraging complementary numerical and physical techniques: sliding-distance-coupled finite element analysis (Iowa) and servo-controlled laboratory simulation (Leeds). Aim 2 is to implement a novel approach to in vivo TDR radiographic wear measurement (Iowa), using high-resolution digital image analysis to assess relative three-dimensional pose position of the implant's metallic end plates. After documenting accuracy/precision, the pose image analysis technique will be used to measure wear in one of the largest/longest-ongoing European TDR series (Munich). Aim 3 is to assess the functional biologic activity of TDR wear debris (Leeds). Morphologically realistic simulator-generated debris will be used to challenge cells in a culture preparation specifically tailored to reflect the local spinal environment, from which key metrics of the inflammatory/osteolytic cascade will be assayed.